The proposed studies will attempt to define the function of a family of lectin-like proteins, designated NKG2, that is expressed primarily on NK cells. All studies will be carried out on two family members, NKG2-A and NKG2-D, that have very different amino acid sequences throughout their lectin domains and, thus, probably have different ligand specificities. cDNA fragments encoding these two proteins will be introduced into a number of procaryotic and eucaryotic expression vectors to create reagents and cell lines for subsequent studies. Polyclonal and monoclonal antibodies will be generated against these expression products. A number of assays are planned to test for the ability of the NKG2 proteins, when bound either by the natural ligand or by anti-NKG2 monoclonal antibodies, to trigger a cytolytic response or deliver a transmembrane signal. These assays will be carried out on an NK cell population and on NKG2-transfected T cell lines. Eucaryotic expression products will also be used to identify cells that express the NKG2 target ligands.